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Updated: Aug 23, 2025

Optimization of the Ugi Reaction Using Parallel Synthesis and Automated Liquid Handling
Published on: November 11, 2008
Closed-loop optimization of general reaction conditions for heteroaryl Suzuki-Miyaura coupling
Nicholas H Angello1,2, Vandana Rathore1,2, Wiktor Beker3
1Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
Abstract:
General conditions for organic reactions are important but rare, and efforts to identify them usually consider only narrow regions of chemical space. Discovering more general reaction conditions requires considering vast regions of chemical space derived from a large matrix of substrates crossed with a high-dimensional matrix of reaction conditions, rendering exhaustive experimentation impractical. Here, we report a simple closed-loop workflow that leverages data-guided matrix down-selection, uncertainty-minimizing machine learning, and robotic experimentation to discover general reaction conditions. Application to the challenging and consequential problem of heteroaryl Suzuki-Miyaura cross-coupling identified conditions that double the average yield relative to a widely used benchmark that was previously developed using traditional approaches. This study provides a practical road map for solving multidimensional chemical optimization problems with large search spaces.
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